Biochemical and molecular mechanisms underlying the chemopreventive efficacy of rosmarinic acid in a rat colon cancer

2016 ◽  
Vol 791 ◽  
pp. 37-50 ◽  
Author(s):  
Karthikkumar Venkatachalam ◽  
Sivagami Gunasekaran ◽  
Nalini Namasivayam
Keyword(s):  
Colon Cancer ◽  
Rosmarinic Acid ◽  
Molecular Mechanisms ◽  
Rat Colon

Rosmarinic acid inhibits DMH-induced cell proliferation in experimental rats

2015 ◽  
Vol 26 (2) ◽  
Author(s):  
Venkatachalam Karthikkumar ◽  
Gunasekaran Sivagami ◽  
Periyasamy Viswanathan ◽  
Namasivayam Nalini
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Rosmarinic Acid ◽  
Colon Carcinogenesis ◽  
Tumor Formation ◽  
Nuclear Antigen ◽  
Rat Colon ◽  
Control Group ◽  
Total Period ◽  
Entire Study

AbstractColon cancer is one of the most common cancers in both men and women. The present study is an effort to unravel the anticarcinogenic effects of rosmarinic acid (RA) in 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. Administration of DMH induces multiple tumors in the rat colon, which mimics human colon cancer.Male Wistar rats were divided into six groups and fed a high-fat diet. Group 1 served as control, group 2 rats were given RA [5 mg/kg body weight (b.w.)] orally every day for a total period of 30 weeks, and groups 3–6 were given weekly injections of DMH (20 mg/kg b.w. subcutaneous) once a week in the groin for the first 15 weeks. In addition to DMH, groups 4–6 received RA at a dose of 5 mg/kg b.w. during the initiation and postinitiation stages, and also throughout the entire study period. Colon tissues were examined histologically; further, the extent of oxidative stress was assessed by measuring lipid peroxidation and antioxidant levels in the colonic mucosa of rats.Macroscopic and microscopic tumors were identified in all the groups that received DMH. The results revealed that supplementation with RA significantly inhibited the tumor formation and tumor multiplicity in DMH-treated rats. RA supplementation to DMH-administered rats significantly reduced the cell proliferation markers, namely, argyrophilic nucleolar organizing regions as well as proliferative cell nuclear antigen labeling index. In addition, RA supplementation reduces the expressions of tumor necrosis factor-α, interlukin-6, and cyclooxygenase-2, and modulates the expression of p65.The above findings clearly underline the chemopreventive efficacy of RA against DMH-induced colon carcinogenesis.

scholarly journals Deacetylase Plus Bromodomain Inhibition Downregulates ERCC2 and Suppresses the Growth of Metastatic Colon Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1438
Author(s):  
Sabeeta Kapoor ◽  
Trace Gustafson ◽  
Mutian Zhang ◽  
Ying-Shiuan Chen ◽  
Jia Li ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Excision Repair ◽  
Critical Role ◽  
Rat Colon ◽  
Precision Oncology ◽  
Metastatic Colon Cancer ◽  
Colon Cancer Cells ◽  
Combination Drug ◽  
Human Colon Cancer

There is growing evidence that DNA repair factors have clinical value for cancer treatment. Nucleotide excision repair (NER) proteins, including excision repair cross-complementation group 2 (ERCC2), play a critical role in maintaining genome integrity. Here, we examined ERCC2 expression following epigenetic combination drug treatment. Attention was drawn to ERCC2 for three reasons. First, from online databases, colorectal cancer (CRC) patients exhibited significantly reduced survival when ERCC2 was overexpressed in colon tumors. Second, ERCC2 was the most highly downregulated RNA transcript in human colon cancer cells and rat tumors after treatment with the histone deacetylase 3 (HDAC3) inhibitor sulforaphane (SFN) plus JQ1, which is an inhibitor of the bromodomain and extraterminal domain (BET) family. Third, as reported here, RNA-sequencing of polyposis in rat colon (Pirc) polyps following treatment of rats with JQ1 plus 6-methylsulfinylhexyl isothiocyanate (6-SFN) identified Ercc2 as the most highly downregulated gene. The current work also defined promising second-generation epigenetic drug combinations with enhanced synergy and efficacy, especially in metastasis-lineage colon cancer cells cultured as 3D spheroids and xenografts. This investigation adds to the growing interest in combination approaches that target epigenetic ‘readers’, ‘writers’, and ‘erasers’ that are deregulated in cancer and other pathologies, providing new avenues for precision oncology and cancer interception.

Nutrigenomics and Life Style Facet- A Modulatory Molecular Evidence in Progression of Breast and Colon Cancer with Emerging Importance

2021 ◽  
Vol 21 ◽  
Author(s):  
Suman Kumar Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Colon Cancer ◽  
Molecular Mechanisms ◽  
Health Management ◽  
Vital Role ◽  
Molecular Evidence ◽  
Nutritional Interventions ◽  
Phenotypic Alteration ◽  
The Individual ◽  
Supplement Intake

: Legitimate nutrition assumes a significant role in preventing diseases and, in this way, nutritional interventions establish vital strategies in the area of public health. Nutrigenomics centres on the different genes and diet in an individual and how an individual’s genes influence the reaction to bioactive foodstuff. It targets considering the genetic and epigenetic interactions with nutrients to lead to a phenotypic alteration and consequently to metabolism, differentiation, or even apoptosis. Nutrigenomics and lifestyle factors play a vital role in health management and represent an exceptional prospect for the improvement of personalized diets to the individual at risk of developing diseases like cancer. Concerning cancer as a multifactorial genetic ailment, several aspects need to be investigated and analysed. Various perspectives should be researched and examined regarding the development and prognosis of breast and colon cancer. Malignant growth occurrence is anticipated to upsurge in the impending days, and an effective anticipatory strategy is required. The effect of dietary components, basically studied by nutrigenomics, looks at gene expression and molecular mechanisms. It also interrelates bioactive compounds and nutrients because of different 'omics' innovations. Several preclinical investigations demonstrate the pertinent role of nutrigenomics in breast and colon cancer, and change of dietary propensities is conceivably a successful methodology for reducing cancer risk. The connection between the genomic profile of patients with breast or colon cancer and their supplement intake, it is conceivable to imagine an idea of personalized medicine, including nutrition and medicinal services.

scholarly journals Molecular subtype-specific responses of colon cancer cells to the SMAC mimetic Birinapant

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Michael Fichtner ◽  
Emir Bozkurt ◽  
Manuela Salvucci ◽  
Christopher McCann ◽  
Katherine A. McAllister ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Caspase 8 ◽  
Colon Cancer Cells ◽  
Apoptosis Pathway ◽  
Iap Antagonist

AbstractColorectal cancer is a molecularly heterogeneous disease. Responses to genotoxic chemotherapy in the adjuvant or palliative setting vary greatly between patients, and colorectal cancer cells often resist chemotherapy by evading apoptosis. Antagonists of an inhibitor of apoptosis proteins (IAPs) can restore defective apoptosis signaling by degrading cIAP1 and cIAP2 proteins and by inhibition of XIAP. Due to the multiple molecular mechanisms-of-action of these targets, responses to IAP antagonist may differ between molecularly distinct colon cancer cells. In this study, responses to the IAP antagonist Birinapant and oxaliplatin/5-fluorouracil (5-FU) were investigated in 14 colon cancer cell lines, representing the consensus molecular subtypes (CMS). Treatment with Birinapant alone did not result in a substantial increase in apoptotic cells in this cell line panel. Annexin-V/PI assays quantified by flow cytometry and high-content screening showed that Birinapant increased responses of CMS1 and partially CMS3 cell lines to oxaliplatin/5-FU, whereas CMS2 cells were not effectively sensitized. FRET-based imaging of caspase-8 and -3 activation validated these differences at the single-cell level, with CMS1 cells displaying sustained activation of caspase-8-like activity during Birinapant and oxaliplatin/5-FU co-treatment, ultimately activating the intrinsic mitochondrial apoptosis pathway. In CMS2 cell lines, Birinapant exhibited synergistic effects in combination with TNFα, suggesting that Birinapant can restore extrinsic apoptosis signaling in the context of inflammatory signals in this subtype. To explore this further, we co-cultured CMS2 and CMS1 colon cancer cells with peripheral blood mononuclear cells. We observed increased cell death during Birinapant single treatment in these co-cultures, which was abrogated by anti-TNFα-neutralizing antibodies. Collectively, our study demonstrates that IAP inhibition is a promising modulator of response to oxaliplatin/5-FU in colorectal cancers of the CMS1 subtype, and may show promise as in the CMS2 subtype, suggesting that molecular subtyping may aid as a patient stratification tool for IAP antagonists in this disease.

scholarly journals Effects of Watermelon Consumption on Cellular Proliferation, and Apoptosis in Rat Colon (P05-019-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Meseret Fesseha ◽  
Mee Young Hong
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cellular Proliferation ◽  
Dietary Intervention ◽  
Citrullus Lanatus ◽  
Proliferation Index ◽  
Cancer Center ◽  
Rat Colon ◽  
Proliferative Zone ◽  
Proliferation And Apoptosis

Abstract Objectives Colon Cancer is the second deadliest cancerous disease worldwide among men and women. It has been estimated that more than half of colon cancers may be preventable by dietary intervention. A disturbance of the homeostasis between cellular proliferation and apoptosis is associated with colon cancer development. Watermelon (Citrullus lanatus) is rich in L-citrulline, a precursor of L-arginine. It has been shown that L-arginine may have anti-inflammatory roles and serves as a substrate for synthesis of nitric oxide, which in turn exerts wide-ranging physiological effects including tumoricidal effects via modification of cell kinetics. Our research examined if colon cancer can be prevented with the supplementation of watermelon powder by lowering cellular proliferation but enhancing apoptosis. Methods In order to test the hypothesis, 21-days old 32 Sprague Dawley rats were allocated to three groups; control, L- arginine (0.36% L-arginine) and watermelon powder (0.5%, w/w). Carcinogen azoxymethane was injected at week 4 and 5, and colon tissues were harvested at 5 week after the 2nd carcinogen injection. Cell proliferation and apoptosis were enumerated using a quantitative immunohistochemical analysis of Ki-67 antibody and TUNEL assay, respectively. Results Cell proliferation was mainly located bottom of colonic crypt (P < 0.05). Apoptotic cells were mostly located in the upper part of crypt (P < 0.05). L-arginine and watermelon fed rats lowered cell proliferation index and proliferative zone (P < 0.05). However, no difference was found on apoptosis among the three groups. Conclusions These results suggest that watermelon powder supplementation may reduce the risk of colon cancer by reducing cell proliferation rather than alteration of apoptosis. Further study will follow to determine the mechanism of anti-proliferative effect of watermelon supplementation. Funding Sources National Watermelon Promotion Board; SDSU/UCSD Cancer Center Partnership Scholars Program.

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